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Nano-TiO2 induces autophagy to protect against cell death through antioxidative mechanism in podocytes

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Abstract

Autophagy is a cellular pathway involved in degradation of damaged organelles and proteins in order to keep cellular homeostasis. It plays vital role in podocytes. Titanium dioxide nanoparticles (nano-TiO2) are known to induce autophagy in cells, but little has been reported about the mechanism of this process in podocytes and the role of autophagy in podocyte death. In the present study, we examined how nano-TiO2 induced authophagy. Besides that, whether autophagy could protect podocytes from the damage induced by nano-TiO2 and its mechanism was also investigated. Western blot assay and acridine orange staining presented that nano-TiO2 significantly enhanced autophagy flux in podocytes. In addition, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were involved in such process. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that upregulated level of autophagy induced by rapamycin in high concentration nano-TiO2-treated podocytes could significantly reduce the level of oxidative stress and alleviate podocyte death. Downregulating the level of autophagy with 3-methyladenine had the opposite effects. These findings indicate that nano-TiO2 induces autophagy through activating AMPK to inhibit mTOR in podocytes, and such autophagy plays a protecting role against oxidative stress on the cell proliferation. Changing autophagy level may become a new treatment strategy to relieve the damage induced by nano-TiO2 in podocytes.

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Acknowledgments

This work was supported by grant from the National Natural Science Foundation of China (31271074, 81571804) and the National Basic Research Program of China (2011CB944003).

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Authors and Affiliations

  1. College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, China

    Xiaochen Zhang, Hongqiang Yin, Zhigui Li & Zhuo Yang

  2. College of Life Sciences, Nankai University, Tianjin, 300071, China

    Tao Zhang

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  1. Xiaochen Zhang
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  2. Hongqiang Yin
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  3. Zhigui Li
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  4. Tao Zhang
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  5. Zhuo Yang
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Correspondence to Zhuo Yang.

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Zhang, X., Yin, H., Li, Z. et al. Nano-TiO2 induces autophagy to protect against cell death through antioxidative mechanism in podocytes. Cell Biol Toxicol 32, 513–527 (2016). https://doi.org/10.1007/s10565-016-9352-y

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